The key limiting factor in cancer excision for cure is the costly and time consuming ascertainment of negative surgical margins by Mohs surgery with frozen section histology. We propose video assisted micrographic surgery (VAMS) as a new paradigm to guide microscopic surgery to improve outcomes and patient experience in skin cancer excision. Although line scanning confocal microscopy may usefully guide surgical excisions, we propose to develop and implement a tri-modal line scanning version to deliver real-time margin status. We will evaluate the system first in non-interventional studies, and then interventional clinical trials in a high volume skin cancer surgery practice. We propose to ultimately transform curative cancer surgery. Potential for cure resides in the ability to achieve tumor free plane i.e. clear surgical margins. Gold standard for confirmation of clear margins is achieved by evaluating sections stained with hematoxylin and eosin. Difficulties arise in cases of extensive cancers requiring multiple excisions. This leads to increased operative time, cost and potential perioperative morbidity. We propose to refine and translate the use of a novel confocal trimodal device that allows direct visualization of the entire peripheral and deep margin of the excised specimen in under 3 minutes. This has the potential to decrease total operative time by at 85% to 95% in cases where initial excision specimen shows margin positivity. We will begin by working with nonmelanoma skin cancer and evaluating sensitivity, specificity of the trimodal device for margin control in Mohs micrographic surgery. The modification will transform Mohs surgery into Video Assisted Micrographic Surgery (VAMS). We will also define differences in operative time and decreased cost resulting from use VAMS vs. Mohs for complex cancers requiring more than one excision. Confocal devices have been used to evaluate nonmelanoma skin cancer. However we propose the first interventional clinical trial in the United States to evaluate use of this methodology. This has not yet been done in the United States because of the time required to generate high quality confocal images quickly.